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We recently reported that a 4% high-salt diet + saline for drinking (HS + saline) leads to a catabolic state, reduced heart rate, and suppression of cardiovascular energy expenditure in mice. We suggested that HS + saline reduces heart rate via the suppression of the sympathetic nervous system to compensate for the high salt intake-induced catabolic state. To test this hypothesis, we directly measured renal sympathetic nerve activity (RSNA) in conscious Sprague-Dawley (SD) rats using a radiotelemetry system. We confirmed that HS + saline induced a catabolic state. HS + saline decreased heart rate, while also reducing RSNA in SD rats. In contrast, Dahl salt-sensitive (DSS) rats exhibited no change in heart rate and increased RSNA during high salt intake. Renal denervation significantly decreased heart rate and attenuated the catabolic state independent of blood pressure in DSS rats fed HS + saline, suggesting that salt-sensitive animals were unable to decrease cardiovascular energy consumption due to abnormal renal sympathetic nerve activation during high salt intake. These findings support the hypothesis that RSNA mediates heart rate during high salt intake in SD rats. However, the insensitivity of heart rate and enhanced RSNA observed in DSS rats may be additional critical diagnostic factors for salt-sensitive hypertension. Renal denervation may benefit salt-sensitive hypertension by reducing its effects on catabolism and cardiovascular energy expenditure.

Total nephron counts vary widely between individuals and may affect susceptibility to certain diseases, including hypertension and chronic kidney disease. Detailed analyses of whole kidneys collected from autopsy patients remain the only method for accurately counting nephrons in humans, with no equivalent option in living subjects. Current technological advances have enabled estimations of nephron numbers in vivo, particularly the use of total nephron number and whole-kidney glomerular filtration rate to estimate the mean single-nephron glomerular filtration rate. The use of this method would allow physicians to detect dynamic changes in filtration function at the single-nephron level rather than to simply count the number of nephrons that appear to be functioning. Currently available methods for estimating total nephron number in clinical practice have the potential to overcome limitations associated with autopsy analyses and may therefore pave the way for new therapeutic interventions and improved clinical outcomes.

BackgroundRecent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination.MethodsWe conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination.ResultsIn the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction.ConclusionThis study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice.

IntroductionDenosumab, a fully human anti-RANKL monoclonal antibody, is a widely used osteoporosis treatment that is increasingly being used in patients undergoing dialysis; however, its long-term efficacy and safety in these patients remain unknown.Materials and methodsThis observational study comprised individuals aged ≥ 20 years undergoing hemodialysis and receiving denosumab. After denosumab administration, we analyzed the long-term changes in bone mineral density (BMD) and levels of bone turnover markers (BTMs) and calcium.ResultsThe study included 45 patients who have been receiving denosumab for a median duration of 3.8 (interquartile range, 2.5–6.7) years. Tartrate-resistant acid phosphatase 5b (TRACP-5b) levels decreased from a median of 595 (434–778) mU/dL at baseline to 200 (141–430) mU/dL after 6 months of denosumab administration (P < 0.001) and remained low thereafter. Similarly, bone-specific alkaline phosphatase (BAP) levels decreased from a median of 18.2 (15.9–25.8) μg/L at baseline to 12.4 (9.9–15.6) μg/L after 6 months (P < 0.001) and remained low thereafter. Meanwhile, BMD, as assessed with dual energy X-ray absorptiometry and measured at the distal 1/3 of the radius, did not decrease (0.465 ± 0.112 g/cm2 at baseline vs. 0.464 ± 0.112 g/cm2 after administration; P = 0.616). Regarding hypocalcemia, corrected calcium levels reached were the lowest at 7 days after administration and normalized within 30 days.ConclusionThe study showed long-term suppression of TRACP-5b and BAP levels and sustaining BMD after denosumab administration over an extended period in patients undergoing hemodialysis.

Background Finerenone has been shown to exert renoprotective effects in patients with diabetic kidney disease. However, the effects of finerenone on proteinuria and serum potassium levels in patients already receiving renin–angiotensin system inhibitors and sodium-glucose cotransporter 2 inhibitors have not been fully elucidated. Methods A total of 47 patients with diabetic kidney disease already treated with angiotensin receptor blocker, angiotensin-converting-enzyme inhibitor or angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors and newly started treatment with finerenone were analyzed to identify predictors of finerenone-induced changes in proteinuria and serum potassium levels. Results After 57.8 ± 25.3 days of treatment with finerenone, urinary protein was significantly decreased from 2.61 ± 2.34 g/gCr to 2.29 ± 2.44 g/gCr and serum potassium was significantly elevated from 4.27 ± 0.36 mmol/L to 4.47 ± 0.42 mmol/L, respectively. There were no patients whose serum potassium levels reached 5.5 mmol/L. The amount of estimated sodium excretion was significantly correlated with the finerenone-induced changes in proteinuria and was the only significant predictive factor for the proteinuria-reducing effect of finerenone. Lower baseline serum potassium level was associated with a greater increase in serum potassium levels after finerenone administration. Conclusions Proteinuria-lowering effect of finerenone may be influenced by the amount of sodium intake in patients with diabetic kidney disease.

[This corrects the article DOI: 10.1371/journal.pone.0309657.].

BackgroundAlthough zinc deficiency is common among dialyzed patients, its prevalence among non-dialyzed subjects and its relationship to renal function remain unclear.MethodsWe selected 816 non-dialyzed subjects (495 males; mean age, 56 ± 18 years) who underwent measurement of serum zinc at Jikei University Hospital between April 2018 and March 2019 using the Standardized Structured Medical Information eXchange2 (SS-MIX2) system, a global standard in Japan that enables collection of structured medical records with automatic data transfer to a registry database system. A serum zinc level of 60–80 μg/dL was defined as marginal zinc deficiency and a level of < 60 μg/dL as absolute zinc deficiency. We investigated factors associated with serum zinc using multiple regression analysis.ResultsMarginal and absolute zinc deficiency were present in 52.3% and 30.6% of subjects, respectively. Serum zinc levels tended to decrease with increasing stage of chronic kidney disease (CKD) (P = 0.051). Estimated glomerular filtration rate (eGFR) was not independently associated with serum zinc levels. Instead, serum albumin (t = 4.69, P < 0.01), hemoglobin (t = 2.54, P = 0.01) and mean corpuscular volume (MCV) (t = − 2.20, P = 0.03) were independently associated with serum zinc. In sensitivity analyses, serum zinc was not associated with either serum copper- or iron-related parameters.ConclusionThis large-scale study clarified the prevalence of zinc deficiency among non-dialyzed Japanese subjects. In addition, eGFR was not independently associated with serum zinc, probably due to confounding factors, such as nutritional status and degree of anemia. Further investigations are needed to clarify the epidemiology of zinc deficiency and its associations with CKD.

Fatigue is one of the most frequent complications in dialyzed patients and is associated with poorer patient outcomes. Multiple factors are reported to be associated with fatigue development. Of them, the impacts of dialysis modalities remain unknown. A total of 194 dialysis patients (mean age, 61±11 years; 134 males; modalities included hemodialysis (HD) in 26, online hemodiafiltration (HDF) in 74, peritoneal dialysis (PD) in 68, and combined therapy with PD and HD in 26 cases) were recruited for this cross-sectional study. Fatigue was assessed using the Profile of Mood States (POMS), a Visual Analogue Scale (VAS), and our original scale of fatigue, and depression was assessed by the Beck Depression Inventory-second edition (BDI-II). Our original scale of fatigue was administered both on dialysis and dialysis-free days to patients on HD and online HDF. The scores of the POMS, VAS, and our original scale were weakly but significantly inter-related (rho = 0.58, P<0.01; rho = 0.47, P<0.01, and rho = 0.42, P<0.01 between POMS and VAS, POMS and our original scale for fatigue, and VAS and our original scale for fatigue, respectively). The scores of these 3 tests showed no significant differences among the 4 modalities. On multivariate analysis, age, body mass index, creatinine, and employment status were associated with the presence or severity of fatigue, whereas dialysis modality was not. A similar result was obtained in 122 patients without depression. The prevalence of fatigue by our original scale was significantly lower on dialysis-free days than on dialysis days in patients on HD and online HDF. The results suggest that there is no significant association between different dialysis modalities including HD, online HDF, PD and combined therapy with PD and HD and the prevalence or severity of fatigue.

[This corrects the article DOI: 10.1371/journal.pone.0250581.].[This corrects the article DOI: 10.1371/journal.pone.0250581.].

Since 2008, the Japanese government has started measures against chronic kidney disease (CKD), and steady changes have been achieved, including a decrease in the age-adjusted rate of new dialysis introduction. However, the total number of dialysis patients has not declined because of the progression of aging. Therefore, the Japanese government has started more concrete measures since 2018. It aims to prevent CKD exacerbation mainly by early referrals to nephrologists using “criteria for referral from a primary care physician to a kidney specialist/specialized medical institution”. In addition, key performance indicators are set to reduce the number of new dialysis patients from 39,000 in 2016 to ≤ 35,000 by 2028. We hope that you can refer to this measure all over the world and proceed with CKD measures. This report has been originally notified from the Ministry of Health, Labor and Welfare in Japanese. This is the English version of it.